Worldwide, more than l,000,000 partial and total hip and knee replacement prostheses are inserted per year, and titanium and its alloys are the metals of choice in the majority of the new implant concepts. The unprecedented rise in the use of this one material system is the result of widespread belief of excellent in vivo tolerance. Specifically, when the local tissue interaction between titanium and the host was analyzed, a favorable histological assessment emerged. Yet, new clinical data as well as recent biological experimentation revealed unanticipated phenomena and is therefore suggestive of possible adverse reactions. Especially wear and histiocytic response associated with joint prostheses, and large specific surface area of the particulate wear debris warrants reaching for a comprehensive understanding of the interaction between titanium based alloys and the physiological environment. This represents the long term objective of this application. Our recent data suggest that, in vitro in the absence of wear, titanium is released as a titanium hydroxide or a titanium hydrogen phosphate, and not as a reactive ion. In parallel with the dissolution there is an oxidation. The corollary is, as we hypothesize, that the products released in vivo without wear must accumulate locally. Furthermore they are transported systemically only to a limited extent In an ongoing study to be finished within one year, release and accumulation patterns are determined by measuring titanium concentrations in local tissues, serum, urine and distant organs. When there is wear, it is only one of the two factors that affect the behavior of the metal, the purely electrochemical release being the other factor. It is our second hypothesis then, that in the presence of relative motion, its effects are additive to the electrochemical release, thereby affecting the oxide structure. This leads to enhanced dissolution and oxidation, and causes the formation of oxide asperities, which subsequently shear off. They represent the particulate debris commonly found in tissues. These phenomena are analyzed in vitro. Surface analysis, including scanning tunnelling microscopy with atomic resolution is an important component in this study. The third hypothesis states that increased elemental metal burden in serum or urine of patients is due to enhanced release at metal to metal interfaces experiencing relative motion. Thus, we propose a prospective, longitudinal study with well controlled implants with or without metal to metal interfaces to support this hypothesis. The understanding of the relationship between release and wear phenomena generated by this study, will support the safe use of current titanium based implants, aid in interpreting clinical data and provide a basis for new and improved surgical devices.